O00337 (S28A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium/nucleoside cotransporter 1

Alternative name(s):
Concentrative nucleoside transporter 1
Short name=CNT 1
Short name=hCNT1
Na(+)/nucleoside cotransporter 1
Sodium-coupled nucleoside transporter 1
Solute carrier family 28 member 1

Gene names

Name:	SLC28A1
Synonyms:	CNT1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	649 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine). It also transports the antiviral pyrimidine nucleoside analogs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). It may be involved in the intestinal absorption and renal handling of pyrimidine nucleoside analogs used to treat acquired immunodeficiency syndrome (AIDS). It has the following selective inhibition: adenosine, thymidine, cytidine, uridine >> guanosine, inosine.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in kidney.
Polymorphism	Three variant forms of isoform 1 (A, B and C) are expressed in the kidney. All three variant forms have similar nucleoside transport activity.
Sequence similarities	Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family. [View classification]

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nucleobase-containing compound metabolic process Traceable author statement Ref.1. Source: ProtInc nucleoside transport Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	nucleoside binding Inferred from electronic annotation. Source: InterPro nucleoside transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc nucleoside:sodium symporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00337-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O00337-2)

The sequence of this isoform differs from the canonical sequence as follows:
     155-175: GLALAAFLGLVLWLSLDTSQR → DPRPWSKEGPNQYLPQITWTV
     176-649: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 649	649	Sodium/nucleoside cotransporter 1		PRO_0000070446
Regions
	Topological domain	1 – 80	80	Cytoplasmic Potential
	Transmembrane	81 – 104	24	Helical; Potential
	Topological domain	105 – 109	5	Extracellular Potential
	Transmembrane	110 – 128	19	Helical; Potential
	Topological domain	129 – 147	19	Cytoplasmic Potential
	Transmembrane	148 – 167	20	Helical; Potential
	Topological domain	168 – 178	11	Extracellular Potential
	Transmembrane	179 – 195	17	Helical; Potential
	Topological domain	196 – 201	6	Cytoplasmic Potential
	Transmembrane	202 – 222	21	Helical; Potential
	Topological domain	223 – 261	39	Extracellular Potential
	Transmembrane	262 – 283	22	Helical; Potential
	Topological domain	284 – 294	11	Cytoplasmic Potential
	Transmembrane	295 – 318	24	Helical; Potential
	Topological domain	319 – 337	19	Extracellular Potential
	Transmembrane	338 – 360	23	Helical; Potential
	Topological domain	361 – 366	6	Cytoplasmic Potential
	Transmembrane	367 – 386	20	Helical; Potential
	Topological domain	387 – 423	37	Extracellular Potential
	Transmembrane	424 – 446	23	Helical; Potential
	Topological domain	447 – 457	11	Cytoplasmic Potential
	Transmembrane	458 – 479	22	Helical; Potential
	Topological domain	480 – 534	55	Extracellular Potential
	Transmembrane	535 – 558	24	Helical; Potential
	Topological domain	559 – 569	11	Cytoplasmic Potential
	Transmembrane	570 – 592	23	Helical; Potential
	Topological domain	593 – 649	57	Extracellular Potential
	Compositional bias	609 – 612	4	Poly-Ser
Amino acid modifications
	Glycosylation	605	1	N-linked (GlcNAc...) Potential
	Glycosylation	643	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	155 – 175	21	GLALA…DTSQR → DPRPWSKEGPNQYLPQITWT V in isoform 2.		VSP_037221
	Alternative sequence	176 – 649	474	Missing in isoform 2.		VSP_037222
	Natural variant	34	1	E → G in A. Ref.1 Ref.2		VAR_009499
	Natural variant	140	1	L → LV in A. Ref.1 Ref.5		VAR_009500
	Natural variant	189	1	V → I in A. Ref.1 Ref.3 Corresponds to variant rs2290272 [ dbSNP | Ensembl ].		VAR_009501
	Natural variant	190	1	A → S. Corresponds to variant rs45523532 [ dbSNP | Ensembl ].		VAR_057194
	Natural variant	237	1	Q → K. Corresponds to variant rs8187758 [ dbSNP | Ensembl ].		VAR_057195
	Natural variant	409	1	N → S in B. Ref.1		VAR_009502
	Natural variant	510	1	R → C. Ref.5 Corresponds to variant rs2242047 [ dbSNP | Ensembl ].		VAR_057196
	Natural variant	521	1	D → N in B and C. Ref.1 Ref.3 Corresponds to variant rs2242046 [ dbSNP | Ensembl ].		VAR_009503
	Natural variant	546	1	S → P. Corresponds to variant rs45584739 [ dbSNP | Ensembl ].		VAR_061802
Experimental info
	Mutagenesis	318	1	S → G: Enables transport of purine nucleosides. Ref.6
	Mutagenesis	319	1	Q → M: Increases transport of purine nucleosides; when associated with Gly-319. Ref.6
	Mutagenesis	352	1	S → T: Produces a full purine-type transporter; when associated with Gly-319 and Met-320. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 42E952443B46B102	FASTA	649	71,584
	10 20 30 40 50 60 MENDPSRRRE SISLTPVAKG LENMGADFLE SLEEGQLPRS DLSPAEIRSS WSEAAPKPFS 70 80 90 100 110 120 RWRNLQPALR ARSFCREHMQ LFRWIGTGLL CTGLSAFLLV ACLLDFQRAL ALFVLTCVVL 130 140 150 160 170 180 TFLGHRLLKR LLGPKLRRFL KPQGHPRLLL WFKRGLALAA FLGLVLWLSL DTSQRPEQLV 190 200 210 220 230 240 SFAGICVFVA LLFACSKHHC AVSWRAVSWG LGLQFVLGLL VIRTEPGFIA FEWLGEQIRI 250 260 270 280 290 300 FLSYTKAGSS FVFGEALVKD VFAFQVLPII VFFSCVISVL YHVGLMQWVI LKIAWLMQVT 310 320 330 340 350 360 MGTTATETLS VAGNIFVSQT EAPLLIRPYL ADMTLSEVHV VMTGGYATIA GSLLGAYISF 370 380 390 400 410 420 GIDATSLIAA SVMAAPCALA LSKLVYPEVE ESKFRREEGV KLTYGDAQNL IEAASTGAAI 430 440 450 460 470 480 SVKVVANIAA NLIAFLAVLD FINAALSWLG DMVDIQGLSF QLICSYILRP VAFLMGVAWE 490 500 510 520 530 540 DCPVVAELLG IKLFLNEFVA YQDLSKYKQR RLAGAEEWVG DRKQWISVRA EVLTTFALCG 550 560 570 580 590 600 FANFSSIGIM LGGLTSMVPQ RKSDFSQIVL RALFTGACVS LVNACMAGIL YMPRGAEVDC 610 620 630 640 MSLLNTTLSS SSFEIYQCCR EAFQSVNPEF SPEALDNCCR FYNHTICAQ
	Isoform 2 [UniParc]. Checksum: 34C7DD93D84F60EE	FASTA	175	20,180
	10 20 30 40 50 60 MENDPSRRRE SISLTPVAKG LENMGADFLE SLEEGQLPRS DLSPAEIRSS WSEAAPKPFS 70 80 90 100 110 120 RWRNLQPALR ARSFCREHMQ LFRWIGTGLL CTGLSAFLLV ACLLDFQRAL ALFVLTCVVL 130 140 150 160 170 TFLGHRLLKR LLGPKLRRFL KPQGHPRLLL WFKRDPRPWS KEGPNQYLPQ ITWTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1)." Ritzel M.W.L., Yao S.Y.M., Huang M.-Y., Elliott J.F., Cass C.E., Young J.D. Am. J. Physiol. 272:C707-C714(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS A GLY-34; VAL-140 INS AND ILE-189, VARIANTS B SER-409 AND ASN-521, VARIANT C ASN-521. Tissue: Kidney.
[2]	"Genomic organization and sequence of the gene encoding the human sodium-dependent, pyrimidine-selective nucleoside transporter (CNT1)." Ritzel M.W.L., Ritzel R.G., Cass C.E., Young J.D. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT A GLY-34.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT A ILE-189, VARIANT B ASN-521, VARIANT C ASN-521. Tissue: Small intestine.
[4]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS A VAL-140 INS AND CYS-510. Tissue: Colon.
[6]	"Identification of amino acid residues responsible for the pyrimidine and purine nucleoside specificities of human concentrative Na(+) nucleoside cotransporters hCNT1 and hCNT2." Loewen S.K., Ng A.M.L., Yao S.Y.M., Cass C.E., Baldwin S.A., Young J.D. J. Biol. Chem. 274:24475-24484(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF SER-318; GLN-319 AND SER-352.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U62966 mRNA. Translation: AAB53837.1. U62967 mRNA. Translation: AAB53838.1. U62968 mRNA. Translation: AAB53839.1. AF187978 , AF187969, AF187970, AF187971, AF187972, AF187973, AF187974, AF187975, AF187976, AF187977 Genomic DNA. Translation: AAF15353.1. AK291997 mRNA. Translation: BAF84686.1. AC087468 Genomic DNA. No translation available. AC103741 Genomic DNA. No translation available. BC029788 mRNA. Translation: AAH29788.1. BC039898 mRNA. Translation: AAH39898.1. BC126204 mRNA. Translation: AAI26205.1. BC126206 mRNA. Translation: AAI26207.1.
IPI	IPI00011289. IPI00402760.
RefSeq	NP_004204.3. NM_004213.3. NP_964014.1. NM_201651.1.
UniGene	Hs.459187.
3D structure databases
ProteinModelPortal	O00337.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000286749.
Protein family/group databases
TCDB	2.A.41.2.3. concentrative nucleoside transporter (CNT) family.
PTM databases
PhosphoSite	O00337.
Proteomic databases
PaxDb	O00337.
PRIDE	O00337.
Protocols and materials databases
DNASU	9154.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000286749; ENSP00000286749; ENSG00000156222. ENST00000338602; ENSP00000341629; ENSG00000156222. ENST00000394573; ENSP00000378074; ENSG00000156222.
GeneID	9154.
KEGG	hsa:9154.
UCSC	uc002blf.3. human. uc002blg.3. human.
Organism-specific databases
CTD	9154.
GeneCards	GC15P085427.
HGNC	HGNC:11001. SLC28A1.
HPA	HPA019551.
MIM	606207. gene.
neXtProt	NX_O00337.
PharmGKB	PA387.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1972.
HOVERGEN	HBG054073.
InParanoid	O00337.
KO	K11536.
OMA	SWRTVSW.
OrthoDB	EOG4V170B.
PhylomeDB	O00337.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	O00337.
Bgee	O00337.
CleanEx	HS_SLC28A1.
Genevestigator	O00337.
GermOnline	ENSG00000156222. Homo sapiens.
Family and domain databases
InterPro	IPR008276. C_nuclsd_transpt. IPR018270. C_nuclsd_transpt_met_bac. IPR011657. Nucleos_tra2_C. IPR011642. Nucleoside_recog_Gate. IPR002668. Nuclsd_transpt2. [Graphical view]
PANTHER	PTHR10590. PTHR10590. 1 hit.
Pfam	PF07670. Gate. 1 hit. PF07662. Nucleos_tra2_C. 1 hit. PF01773. Nucleos_tra2_N. 1 hit. [Graphical view]
TIGRFAMs	TIGR00804. nupC. 1 hit.
ProtoNet	Search...
Other
BindingDB	O00337.
ChEMBL	CHEMBL5551.
GenomeRNAi	9154.
NextBio	34343.
SOURCE	Search...

Entry information

Entry name

S28A1_HUMAN

Accession

Primary (citable) accession number: O00337
Secondary accession number(s): A0AV42 , A8K7I2, O00335, O00336, Q5U5S6, Q5U648, Q9UEZ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.